Glioblastoma (GBM; World Health Organization grade IV glioma) is the most common primary brain tumor in adults. Even with aggressive surgical resection using state-of-the-art preoperative and intraoperative neuroimaging along with recent advances in postsurgical radiotherapy and chemotherapy, the prognosis for GBM patients remains dismal. The median survival rate under the current optimum postsurgical treatment protocol is only 15 months (Stupp et al., 2005). The identification of new candidate therapeutics has thus highest priority. One challenge in defining new therapeutic approaches is the heterogeneity of GBMs. An intra-tumoral heterogeneity is derived from genetic and non-genetic epigenetic causes. Also, an emerging concept proposes that heterogeneous tumor cell phenotypes arise from continuing operation of aberrant and malignant differentiation processes initiated by a small subset of stem-like cells. These stem-like cells have are defined by their capacity (i) of self-renewal, (ii) of tumor initiation and propagation in various xenotransplantation paradigms and (iii) multipotency, i.e. their capacity to differentiate into astrocytes, oligodendrocytes and neurons (Singh et al., 2004). In addition, it is presumed that these cells are resistant to most current radio- and chemotherapies, and it is thought that therapies directed against stem-like cells may improve the dreadful record of current conventional therapies (Dirks, 2008; Chalmers, 2007). Based on this view, it has been begun to adapt in vitro technologies commonly applied in the field of stem cell research to isolate, expand, and to better characterize tumor cells with stem cell characteristics (Pardal et al., 2003, Glas et al., 2010). Cells are propagated as a monolayer culture under adhesive conditions, which may offer significant advantages in comparison to “sphereoid” cultures (Lee et al., 2006; Pollard et al., 2009).
Thus, the problem underlying the present invention can be viewed as the provision of novel compounds for the improved chemotherapy of glioblastoma.